Alcoholism is a problem of significant proportion in Alaska and among Alaska Natives in particular. Due to remote nature of Alaska the provision of care is often difficult. Pharmacological adjuncts may provide an important tool for augmenting the effectiveness of existing treatments. Naltrexone, an opioid antagonist, has been shown to be efficacious in preventing relapse among Caucasian and African American patients, but the efficacy of this treatment has not been established in Native populations. In addition, not all patients benefit from naltrexone suggesting that combination pharmacotherapy may be useful, particularly if the additional agent targets a different neurobiological system affected by alcoholism. In this regard, serotonin re-uptake inhibitors (SSRI), which address hypothesized serotonin deficiencies in alcoholism, have been shown to be modestly successful in reducing drinking in heavy drinkers although the response in alcohol dependent subjects has been mixed. However, there are promising preclinical and human preliminary studies suggesting that the combination of naltrexone and an SSRI may be more effective in reducing alcohol consumption than naltrexone alone. As a result, the proposed study has two primary aims: The first is to replicate previous findings in Caucasians and African Americans regarding the ability of naltrexone to reduce the risk of relapse in Alaska Natives with alcohol dependence. The second is to test whether combination therapy with naltrexone and sertraline yields better abstinence rates than monotherapy with naltrexone in this population. The efficacy of these pharmacological interventions will be tested when provided in conjunction with a model of counseling that could be used in remote rural locations. One hundred ninety-eight alcohol dependent individuals of Alaska Native heritage will participate in a double blind, double dummy placebo controlled study and will receive either 1) Combination therapy (naltrexone + sertraline), 2) Naltrexone monotherapy (naltrexone + placebo sertraline) or 3) Placebo (placebo naltrexone + placebo sertraline). Participants will be recruited from the townships of Sitka, Juneau/Ketchikan and village areas and evaluated centrally in Sitka. Participants will receive compliance enhancement, counseling and pharmacotherapy for 12 weeks and followed 6 and 12 months after treatment Secondary aims are to evaluate whether the combination therapy is better tolerated than monotherapy, 2) the durability of improvement during following and 3) the acceptability/implementation of the treatment components.